POS0515 THE POTENTIAL CAUSAL RELATIONSHIP BETWEEN PHYSICAL ACTIVITY, LEISURE SEDENTARY BEHAVIORS, AND GOUT
Authors: J. Y. Chen, Q. Feng, Z. Liu, Q. Yu, P. F. He, X. LI, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Gout is a type of inflammatory arthritis caused by the deposition of monosodium urate crystals onto diverse body joints [1]. Physical activity (PA) can reduce patients' pain caused by gout and Leisure sedentary behaviors (LSB) do harm to even normal people [2]. However, the genetic causality between PA/LSB and gout remains to be seen. <h3>Objectives</h3> In this study, we aimed to systematically evaluate the causal relationship between PA/LSB and gout. <h3>Methods</h3> We performed a two-sample Mendelian Randomization (MR) analysis to investigate the potential causality between PA/LSB and gout susceptibility. PA included five phenotypes: accelerometer-based PA, vigorous physical exercise (VPA), moderate to vigorous physical activity (MVPA), moderate physical activity 10+ minutes, and vigorous physical activity 10+ minutes. The summary data of PA were obtained from a genome-wide association study (GWAS) in UK Biobank [3]. LSB included four phenotypes: time spent watching television (TV), time spent using a computer, time spent driving, and time spent using a mobile phone. And the data of LSB was also derived from the GWAS of the UK Biobank. The gout GWAS (2,115 cases and 67,259 controls) was derived from the Global Urate Genetics Consortium. Single nucleotide polymorphisms (SNPs) that were independent (r2 &lt; 0.001) and strongly related to PA/LSB (p &lt; 1 × 10-7, F&gt;10) were selected as instrumental variables (IVs). Besides, we removed confounding IVs associated with alcohol, neutrophils, and BMI. The inverse variance-weighted (IVW), MR-Egger, and weighted median methods were employed to evaluate the causal effect between PA/LSB and gout. Among them, IVW is the principal method. Pleiotropic and heterogeneity assessment and sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept analysis, and the leave-one-out analysis. <h3>Results</h3> After removing confounders, the causality between genetically predicted accelerometer-assessed PA and risk of gout was indicated by IVW [OR=1.15, 95%CI: 1.02—1.31, p=0.0242]. No obvious causal relationship was observed between other PA/LSB and gout. (P&gt;0.05) MR-Egger and weighted median were consistent with IVW results. No pleiotropy or heterogeneity of the IVs was found. Details of the results are shown in Figure 1. <h3>Conclusion</h3> Our findings supported a causal effect of accelerometer-measured PA on the increased risk of gout. No associations between other PA/LSB and gout were observed. Further research is needed to explore how physical activity affects gout. <h3>References</h3> [1]Dalbeth, N., Choi, H. K., Joosten, L. A. B., Khanna, P. P., Matsuo, H., Perez-Ruiz, F., &amp; Stamp, L. K. (2019). Gout. Nature reviews. Disease primers, 5(1), 69. https://doi.org/10.1038/s41572-019-0115-y [2]Gwinnutt, J. M., Wieczorek, M., Balanescu, A., Bischoff-Ferrari, H. A., Boonen, A., Cavalli, G., de Souza, S., de Thurah, A., Dorner, T. E., Moe, R. H., Putrik, P., Rodríguez-Carrio, J., Silva-Fernández, L., Stamm, T., Walker-Bone, K., Welling, J., Zlatković-Švenda, M. I., Guillemin, F., &amp; Verstappen, S. M. M. (2023). 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Annals of the rheumatic diseases, 82(1), 48–56. https://doi.org/10.1136/annrheumdis-2021-222020 [3]Klimentidis, Y. C., Raichlen, D. A., Bea, J., Garcia, D. O., Wineinger, N. E., Mandarino, L. J., Alexander, G. E., Chen, Z., &amp; Going, S. B. (2018). Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. International journal of obesity (2005), 42(6), 1161–1176. https://doi.org/10.1038/s41366-018-0120-3 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.